Moore Andrew R, Derry Sheena, Straube Sebastian, Ireson-Paine Jocelyn, Wiffen Phillip J
Pain Research and Nuffield Division of Anaesthetics, Nuffield Department of Neurosciences, University of Oxford, The Churchill, Oxford, UK Institute of Occupational, Social and Environmental Medicine, University Medical Center Göttingen, Göttingen, Germany Spreadsheet Factory, Stratfield Road, Oxford, UK.
Pain. 2014 Jan;155(1):14-21. doi: 10.1016/j.pain.2013.08.013. Epub 2013 Aug 19.
A Cochrane review of ibuprofen in acute pain suggested that rapidly absorbed formulations of salts, or features to speed absorption, provided better analgesia than standard ibuprofen as the free acid. We examined several lines of evidence to investigate what benefit derived from fast-acting formulations. A systematic review of the kinetics of oral ibuprofen (30 studies, 1015 subjects) showed that median maximum plasma concentrations of fast-acting formulations occurred before 50 min (29-35 min for arginine, lysine, and sodium salts) compared with 90 min for standard formulations. An updated analysis of clinical trials (over 10,000 patients) showed that fast-acting formulations produced significantly better analgesia over 6h and fewer remedications than standard formulations in both indirect and direct comparisons. In dental studies, 200-mg fast-acting ibuprofen (number needed to treat 2.1; 95% confidence interval 1.9-2.4) was as effective as 400 mg standard ibuprofen (number needed to treat 2.4; 95% confidence interval 2.2-2.5), with faster onset of analgesia. Individual patient data analysis in dental pain demonstrated a strong correlation between more rapid reduction of pain intensity over 0-60 min and better pain relief over 0-6h. Rapid initial reduction of pain intensity was also linked with reduced need for remedication. Fast-acting formulations of ibuprofen demonstrated more rapid absorption, faster initial pain reduction, good overall analgesia in more patients at the same dose, and probably longer-lasting analgesia, but with no higher rate of patients reporting adverse events. Achieving a better analgesic effect with fast-acting nonsteroidal anti-inflammatory drug formulations has important implications for safety. Formulation chemistry is of potential importance for analgesics.
Cochrane关于布洛芬治疗急性疼痛的一项综述表明，盐类的快速吸收制剂或能加速吸收的特性，相较于标准的游离酸布洛芬，能提供更好的镇痛效果。我们研究了多条证据线索，以探究速效制剂能带来哪些益处。一项关于口服布洛芬动力学的系统综述（30项研究，1015名受试者）显示，速效制剂的血浆最大浓度中位数出现在50分钟之前（精氨酸、赖氨酸和钠盐为29 - 35分钟），而标准制剂为90分钟。对临床试验（超过10000名患者）的更新分析表明，在间接和直接比较中，速效制剂在6小时内产生的镇痛效果显著优于标准制剂，且再次用药次数更少。在牙科研究中，200毫克速效布洛芬（治疗所需人数为2.1；95%置信区间1.9 - 2.4）与400毫克标准布洛芬（治疗所需人数为2.4；95%置信区间2.2 - 2.5）效果相当，但镇痛起效更快。对牙科疼痛患者个体数据分析表明，在0 - 60分钟内疼痛强度更快降低与0 - 6小时内更好的疼痛缓解之间存在强相关性。疼痛强度的快速初始降低也与减少再次用药需求相关。布洛芬的速效制剂显示出吸收更快、初始疼痛缓解更快、相同剂量下更多患者有良好的总体镇痛效果且可能镇痛持续时间更长，但报告不良事件的患者比例并未更高。使用速效非甾体抗炎药制剂实现更好的镇痛效果对安全性具有重要意义。制剂化学对于镇痛药可能具有重要意义。
